Seminar 28-11-2015 Prof. J. vd Bergh

•  Meet
The
Professors
(16
clinical/transla5onal;
8
basic)

•  8
Working
Groups

•  1448
Abstracts,
152
Oral
abstracts
(10.8%)

•  115
Late-‐breaking
abstracts,
5
Oral
abstracts
(4.3%)

•  Abstracts
2013:
-‐4%,
2014:
-‐6%,
2015:
-‐2.7%

Highlights
ASBMR
2015

1

§  2015 Abstract handbook
§  Highlights session R. Baron and J. Bilezikian
§  ASBMR website / webcast
§  Notes
§  Published literature
§  IOF congress highlights educational slide set (in agreement with Eli Lilly)
Bronnen
Highlights ASBMR 2015 2

§  Diabetes and bone
§  Fracture and mortality risk
§  Bone strength / bone quality / imaging
§  Vitamin D
§  Bone and Cancer
§  FGF23 - Klotho
Topics

1067 Vertebral Fracture Risk in Diabetic Elderly Men:
The MrOS Study
§  Diabetes is accompanied by increased risk of fracture
§  Patients with T2DM have an increased risk of fracture with
increased BMD compared to controls
§  The increase of hip fracture risk (RR:1.7) in T2DM
§  Data for vertebral fractures (VF), particularly for men are
controversial and limited
INTRODUCTION
T2DM type 2 diabetes mellitus • BMD bone mineral density • VF vertebral fracture
NICOLA NAPOLI ET AL

The MrOS Study
§  Osteoporotic Fractures in Men (MrOS) Study
§  5,994 men (≥65 years)
§  Diabetes (ascertained by self-report, use of diabetes medication or elevated fasting
glucose) was reported in 875 men of whom 80 used insulin
§  Evaluate the prevalence and incidence of VFs in T2DM men compared to their non-DM counterparts
§  Examine whether the association between lumbar spine BMD and VF is similar in T2DM and non-
DM men
SUBJECTS
§  Spine BMD by DXA and QCT
§  Morphometric VFs identified on spine x-rays at baseline and on average 4.6 years later
§  Prevalent VF defined as semi quantitative score (SQ) ≥2
§  Incident VF defined as an increase of ≥1 SQ from baseline
METHODS
VF vertebral fracture • T2DM type 2 diabetes mellitus • BMD bone mineral density • DXA dual x-ray absorptiometry • QCT quantitative computer tomography
NICOLA NAPOLI ET AL.
Highlights ASBMR 20156

The MrOS Study
§  BMD (spine and hip) by DXA and QCT in T2DM compared with controls
§  Bone strength (FEA) increased in T2DM compared with controls
§  Association between decreased BMD (both QCT and DXA) and increased
risk of VF in both groups
§  Absence of increased risk of VF (both prevalent and incident) for patients
with T2DM compared with controls
RESULTS
BMD bone mineral density • DXA dual x-ray absorptiometry • QCT quantitative computer tomography • T2DM type 2 diabetes mellitus • VF vertebral fracture • FEA
finite element analysis • OR odds ratio • BMI body mass index • a areal • OR odds ratio • CI confidence interval
NICOLA NAPOLI ET AL
7

Model
adjusted
for
Prevalent
vertebral
fractures

OR
(95%CI)

Incident
vertebral
fractures

OR
(95%CI)

Model
1:
age,
race,
clinical
site

0.91
(0.74-‐1.18)
1.05
(0.68-‐1.62)

Model
2:
Model
1,
BMI
0.93
(0.70-‐1.25)
1.10
(0.71-‐1.71)

Model
3:
Model
2,
spine
aBMD
1.05
(0.78-‐1.40)
1.28
(0.81-‐2.00)

Model
4:Model
2,
spine
aBMD
1.30
(0.89-‐1.88)
1.40
(0.78-‐2.53)

Reproduced
with
permission

from
the
American
Society
for
Bone
and
Mineral
Research


1067 Vertebral Fracture Risk in Diabetic Elderly Men: The MrOS
Study
NICOLA NAPOLI ET AL
8

§  T2DM is not associated with an increased risk of prevalent or
incident VFs in elderly men
§  Lower BMD is associated with higher risk of prevalent VFs in DM
as well as non-DM men
CONCLUSION

SA0275 Glucose Metabolism Status Is Not Associated With a Recent
History of Falls, Recurrent Falls or Fractures – The Maastricht Study.
§  1577 participants had NGM, 468 had IGM and 908 had T2DM
§  Mean duration 8.7 years, mean HbA1c 52.1 mmol/mol, 21.9%
insulin user.
§  Glucose metabolism status was not significantly associated with
previous fractures and recent falls.
§  In addition, in this cohort of relatively young and well-treated
participants with type 2 diabetes, diabetes severity was not
associated with a previous fractures and recent falls.
CONCLUSION
ELLIS DE WAARD, ANNEMARIE KOSTER, TOM MELAI, TINEKE VAN GEEL, RONALD HENRY, MIRANDA SCHRAM,
PIETER DAGNELIE, CARLA VAN DER KALLEN, SIMONE SEP, COEN STEHOUWER, NICOLAAS SCHAPER, HANS
SAVELBERG, PIET GEUSENS, JOOP VAN DEN BERGH

FR0355 TBS and HbA1c but not BMD are Predictors
of Incident Fractures in Type 1 Diabetes
§  105 individuals (52 males, 53 females)
§  Age 43.6 ± 8.7 years
§  Diabetes duration 21.8 ± 10.4 years
§  Follow-up for 6.9 ± 0.3 years
Investigate potential risk predictors for incident fractures in middle-aged men and women
with long-standing T1D
PARTICIPANTS
§  Associations of traditional risk factors for fractures (e.g. age, gender, family
history of OP and smoking), BMD at LS, FN and TH, TBS and HbA1c with
incident fractures
§  ROC analysis of TBS and HbA1c performed to identify potential threshold
effects on incident fractures
OUTCOMES
AND ANALYSIS
T1D Type 1 diabetes • OP osteoporosis • BMD bone mineral density • LS lumbar spine • FN femoral neck • TH total hip • TBS trabecular bone score • ROC receiver
operating characteristic
THOMAS NEUMANN, MARTIN KEIL, GABRIELE LEHMANN, SABINE LODES, BETTINA
KÄSTNER, THOMAS LEHMANN, MICHAEL KIEHNTOPF, DIDIER HANS, OLIVIER LAMY,
ULRICH-ALFONS MÜLLER, GUNTER WOLF, ALEXANDER SÄMANN, JENA UNIVERSITY
HOSPITAL, GERMANY
10

FR0355 TBS and HbA1c but not BMD are Predictors of Incident
Fractures in Type 1 Diabetes
§  No differences between individuals with or without fracture for age or BMD
§  FRAX® did not identify individuals with incident fractures
§  Individuals with incident fractures had higher HbA1c values and lower mean
TBS scores at baseline; associations confirmed by logistic regression
analysis
§  ROC curves showed that mean TBS score and HbA1c level can
discriminate patients with incident fractures from those without fractures
(AUC 0.72 [95% CI = 0.58-0.86; P=0.003] for combined mean TBS scores
and HbA1c levels)
RESULTS
BMD bone mineral density • LS lumbar spine • FN femoral neck • TH total hip • TBS trabecular bone score • ROC receiver operating characteristic
THOMAS NEUMANN, MARTIN KEIL, GABRIELE LEHMANN, SABINE LODES, BETTINA KÄSTNER, THOMAS LEHMANN,
MICHAEL KIEHNTOPF, DIDIER HANS, OLIVIER LAMY, ULRICH-ALFONS MÜLLER, GUNTER WOLF, ALEXANDER
SÄMANN, JENA UNIVERSITY HOSPITAL, GERMANY

FR0355 TBS and HbA1c but not BMD are Predictors
of Incident Fractures in Type 1 Diabetes
§  The frequency of fractures in T1D is high and not predictable using either
age or BMD
§  Only HbA1c and mean TBS score were independently associated with
incident fracturesCONCLUSION
§  Measures of diabetes control, or of bone microarchitecture and material
strength, and advanced glycation end-products (AGEs – e.g. pentosidine
cross-links) may have a more important role in predicting fracture risk in
women and men with T1D
CLINICAL
IMPACT
T1D Type 1 diabetes • BMD bone mineral density • TBS trabecular bone score • ROC receiver operating characteristic
THOMAS NEUMANN, MARTIN KEIL, GABRIELE LEHMANN, SABINE LODES, BETTINA
KÄSTNER, THOMAS LEHMANN, MICHAEL KIEHNTOPF, DIDIER HANS, OLIVIER LAMY,
ULRICH-ALFONS MÜLLER, GUNTER WOLF, ALEXANDER SÄMANN, JENA UNIVERSITY
HOSPITAL, GERMANY
12

1139 Altered trabecular microarchitecture in youth
with type 1 diabetes mellitus
§  83 girls, 10-16 years old (16 T1DM and 67 controls)
§  Cross-sectional study
§  Minimum 1 year of T1DM
Investigate the degree to which microarchitecture is affected in T1D
PARTICIPANTS
§  HR-pQCT of the distal radius and tibia
§  micro-FE analysis to estimate bone strengthDESIGN
§  DXA
§  HR-pQCT
§  Serum Ca, PTH, 25(OH)D, creatinine, glucose, HgbA1c
§  Urine Ca, creatinine
OUTCOMES
AND ANALYSIS
T1D type 1 diabetes • HR-pQCT high resolution peripheric quantitative computer tomography • FE finite element • BMI body mass index • Ca calcium • P phosphate •
PTH parathyroid hormone
DEBORAH MITCHELL, MARY BOUXSEIN, MADHUSMITA MISRA, MASSACHUSETTS
GENERAL HOSPITAL, UNITED STATES
13

14

§  Matched groups for age, bone age, race, and height
§  Higher weight in T1DM subjects with higher BMI Z-score (p<0.001)
§  No difference for serum Ca, P, 25(OH)D, PTH
§  No difference of Z-scores for aBMD at the spine and total body
§  No difference in cortical porosity
§  Strength is lower in tibia, but not in radius of T1DM
RESULTS
T1D type 1 diabetes • BMI body mass index • Ca calcium • P phosphate • PTH parathyroid hormone

§  Similar aBMD between T1DM and controls
§  Impaired trabecular bone (vBMD and Tb Th) contributes to the fracture risk
in T1DM
§  Early occurrence in the course of the disease
AUTHOR’S
CONCLUSION
T1D type 1 diabetes • a areal • BMD bone mineral density • v volumetric • Tb trabecular • Th thickness
15

Bisphosphonates reduce fracture risk in postmenopausal women
with diabetes: Results from FIT and HORIZON trials.
§  A post hoc subgroup analysis of combined individual-level data from two
randomized placebo controlled trials, the Fracture Intervention Trial (FIT) of
alendronate (ALN) and the Health Outcomes and Reduced Incidence with
Zoledronic Acid (ZOL) Once Yearly-Pivotal Fracture Trial (HORIZON-PFT).Design
ANN SCHWARTZ, ERIC VITTINGHOFF, DOUGLAS C. BAUER, STEVEN R. CUMMINGS, ANDREW GREY, MICHAEL R.
MCCLUNG, NICOLA NAPOLI, IAN R. REID, ANNE L. SCHAFER, ROBERT B. WALLACE, DENNIS M. BLACK
In postmenopausal women with DM and low bone density and/or prevalent vertebral fracture,
bisphosphonates reduce fracture incidence
16

FR0252 Contribution of Lumbar Spine BMD to Fracture risk in
individuals with T-score discordance
§  The femoral neck BMD is best validated of all skeletal sites for fracture risk
prediction
§  The lumbar spine BMD may be falsely elevated due to degenerative disc
disease
§  Degenerative changes can also falsely elevate the femoral neck BMD to a
lesser extent
§  Discordance between the LS and FN sites can impact diagnosis and
fracture risk prediction based on bone densitometry
INTRODUCTION
BMD bone mineral density • LS lumbar spine • FN femoral neck
DUNIA ALARKAWI, DANA BLIUC, TUAN NGUYEN, JOHN EISMAN, JACQUELINE CENTER, GARVAN INSTITUTE OF
MEDICAL RESEARCH, AUSTRALIA

§  2270 women and 1373 men aged 60+ years
Examine the impact of LS BMD on fracture risk, specifically in individuals with lower LS T-
score than FN T-score
PARTICIPANTS
§  Prospective cohort from the Dubbo Osteoporosis Epidemiology Study of
community-dwelling women and menDESIGN
§  LS and FN BMD data at first visit, followed from April 1989 to December
2014OUTCOMES
AND ANALYSIS
LS lumbar spine • BMD bone mineral density • FN femoral neck • SD standard deviation • HR hazard ratio • CI confidence interval

§  LS T-score lower than FN T-score by ≥1 SD (discordant group) in 364
women and 60 men
§  In women with lower LS than FN T-score, each 1 SD lower LS T-score
associated with a 30% increase in fracture risk (HR 1.30, 95% CI 1.19-1.41,
P<0.0001)
§  In men with lower LS T-score than FN, no further increase in fracture risk
§  Discordant women were at greater fx risk for all levels of FN T-score
§  Increased fracture risk more apparent for lower levels of FN T-score and in
older age groups
§  An osteoporotic LS T-score increased ten year absolute fracture risk for
women with either normal or osteopenic FN T-score by ~15%.
RESULTS
LS lumbar spine • FN femoral neck • SD standard deviation • HR hazard ratio • CI confidence interval • fx fracture

§  Significant contribution of lower LS BMD to fracture risk in individuals, over
and above FN BMD
§  Women with lower LS T-score by ≥1 SD than FN T-scores consistently
higher absolute fracture risks regardless of their FN T-scores
§  The risk increased exponentially with lower FN BMD and increasing age
§  LS BMD lower than FN BMD should be incorporated into fracture risk
calculation algorithms at least for women
AUTHOR’S
CONCLUSION
LS lumbar spine • BMD bone mineral density • FN femoral neck • SD standard deviation

1066 Predicting Imminent Risk for Fracture in Patients With
Osteoporosis Using Commercially Insured Claims Data
§  163,186 patients with osteoporosis
§  19.7% with a fracture
Identify risk factors associated with imminent first and subsequent fracture
PARTICIPANTS
§  Retrospective cohort study
§  Patients aged ≥50 years with osteoporosis, a new fragility fracture or no
fracture
DESIGN
§  Risk factors for imminent first fracture identified by logistic regression
models that included >60 potential risk factors assessed in the 12 or 24
months prior to index date
§  Cox proportional hazards regression models used to identify risk factors for
subsequent fracture for up to 12 months following the index fracture
OUTCOMES
AND ANALYSIS
MACHAON BONAFEDE, N SHI, R BARRON, X LI, DB CRITTENDEN, D CHANDLER, THOMSON REUTERS
HEALTHCARE, USA
22

SSRI selective serotonin reuptake inhibitor • CNS central nervous system • CI confidence interval
HEALTHCARE, USA
23

SSRI selective serotonin reuptake inhibitor • CNS central nervous system • CI confidence interval
HEALTHCARE, USA
24
§  Vertebral fracture 1.62
§  Charlston index 3 or 4: 1.22 and 1.26
§  Antidepressant 1.21
§  Each decade after Age 50 1.17
Subsequent
fracture

1145 Hip BMD by DXA Can Reliably Estimate Reduction in Hip Risk
in Osteoporosis Trials: A Meta-Regression
§  14 trials with 73,000 women for hip fx
§  30 trials with >75,000 women for NVFx
Examine the relationship between change in total hip BMD and fracture reductions
PARTICIPANTS
§  Study-level meta-regression
§  Exclusion of trials with <5 hip fxDESIGN
§  Modelling of relationship between estimates of effect of treatment on
change in BMD (active-placebo % difference at study end) and log relative
risk of hip fx and NVFx using linear models weighted by study size
OUTCOMES
AND ANALYSIS
BMD bone mineral density • fx fracture • NVFx non-vertebral fracture
DENNIS BLACK, ERIC VITTINGHOFF, RICHARD EASTELL, MARY BOUXSEIN, CHARLES MCCULLOCH, PEGGY M.
CAWTHON, STEVEN R. CUMMINGS, STEPHANIE L. HARRISON, ANNE DE PAPP, VICTOR DISHY, ANDREAS GRAUER,
URSULA KLAUSE, BRUCE H. MITLAK, BRUCE SCHNEIDER, SANYA FANOUS-WHITAKER, JEFF ZACHWIEJA,
CHIYUAN A. ZHANG, DOUGLAS BAUER ,UCSF DEPT OF EPI AND BIOSTAT, USA
25

26
For 2 drugs with 2% vs 6% hip BMD
effect, model predicted a 10% vs. 59%
reduction for hip fracture

§  Relationships strongest for change in hip BMD predicting hip fracture
(r2=0.57, p<.0001)
§  Weaker relationships non-vertebral (r2=0.14, p=0.004) and vertebral
(r2=0.21) fracture
§  For 2 drugs with 2% vs 6% hip BMD effect, model predicted a 10% vs. 59%
reduction for hip fracture
§  For non-vertebral fracture with 2% or 6% change in BMD reductiosn were
6% vs 21%
RESULTS
BMD bone mineral density • fx fracture • NVFx non-vertebral fracture
DENNIS BLACK, ERIC VITTINGHOFF, RICHARD EASTELL, MARY BOUXSEIN, CHARLES MCCULLOCH, PEGGY M.
CAWTHON, STEVEN R. CUMMINGS, STEPHANIE L. HARRISON, ANNE DE PAPP, VICTOR DISHY, ANDREAS GRAUER,
URSULA KLAUSE, BRUCE H. MITLAK, BRUCE SCHNEIDER, SANYA FANOUS-WHITAKER, JEFF ZACHWIEJA, CHIYUAN
A. ZHANG, DOUGLAS BAUER , UCSF DEPT OF EPI AND BIOSTAT, USA
27

MO0284 Potential Years of Life Lost Following Low-
Trauma Fractures in Canada
§  Administrative database of Canadians over age 50 years with low-trauma
fractures 2007-2011
Estimate the potential years of life lost (PYLL) due to low-trauma fractures in Canada
REGISTRY
§  Low-trauma fractures categorized using ICD-10-CA codes as hip, humerus,
vertebral, distal forearm, other sites and multiple sites fractures
§  Calculations of PYLLs for each age group, sex and fracture type by
adjusting the provincial and sex-based standard life tables estimate of life
expectancy for the increased risk of death associated with a fracture
§  Comparison with PYLL estimates due to other diseases reported by
Statistics Canada in 2007
DESIGN
ANALYSIS
PYLL potential years of life lost
ROBERT B. HOPKINS, JONATHAN D. (RICK) ADACHI, LOUIS BESSETTE, NATASHA BURKE,
JACQUES P. BROWN, WILLIAM D LESLIE, SUZANNE MORIN, ALEXANDRA PAPAIOANNOU,
LOUISA PERICLEOUS, JEAN-ERIC TARRIDE, UNIVERSITY OF MANITOBA, CANADA
29

30

13,809
21,812
36,312
44,462
89,247
104,971
127,560
138,808
159,117
Bronchitis/emphys/asth.[J40-J43 J45-
J46]
Prostate cancer [C61]
HIV disease [B20-B24]
Pneumonia and influenza [J10-J18]
Low trauma fractures age 50+
Cerebrovascular diseases [I60-I69]
Colorectal cancer [C18-C21]
Breast cancer [C50]
All Respiratory diseases [J00-J99]

§  PYLL due to low-trauma fractures was 89,247 years (52,131 years for
women, 37,116 years for men)
§  While being only 23% of fractures, hip fractures accounted for 43% of all
PYLL
§  A hip fracture at ages 50 to 59 years decreases life expectancy by 4.0 years
for women and 3.9 years for men, which corresponds to a loss of 15% of life
expectancy
RESULTS
31
§  Low-trauma fractures are associated with a significant loss of life
expectancy and are a significant burden of illness
§  Strategies to reduce the risk of fracture and improve post-fracture care
should be implemented and optimizedCONCLUSION

SA0289 Mortality risk following incident low-trauma osteoporotic fracture and
subsequent fracture: 15- year prospective data from the Canadian Multicentre
Osteoporosis Study (CaMOS)
§  7689 participants (5526 women and 2163 men) aged ≥50 years
Examine the contribution of individual fracture types on mortality risk over and above
known risk factors for mortality
PARTICIPANTS
§  On-going population-based nation-wide cohort study of Canadians
§  Patients followed for 15 years with scheduled interviews and annual postal
questionnaires
§  Self-identified incident fractures from annual report
§  Deaths ascertained through contact with a family member or obituary review
DESIGN
§  Relative survival analysis used to determine survival of CaMos participantsOUTCOMES
AND ANLYSIS
THACH TRAN, DANA BLIUC, DUNIA ALARKAWI, TUAN NGUYEN, JOHN EISMAN, LISA LANGSETMO, JERILYNN C
PRIOR, ROBERT G JOSSE, STEPHANIE M KAISER, CHRISTOPHER S KOVACS, CLAUDIE BERGER, DAVID GOLTZMAN,
DAVID A HANLEY, JONATHAN ADACHI, TENEKE VAN GEEL, PIET GEUSENS, JOOP VAN DEN BERGH, JACQUELINE
CENTER, GARVAN INSTITUTE OF MEDICAL RESEARCH, AUSTRALIA
32

OP osteoporotic • Fx fracture • RR relative risk • CI confidence interval • SMR standardized mortality ratio
PRIOR, ROBERT G JOSSE, STEPHANIE M KAISER, CHRISTOPHER S KOVACS, CLAUDIE BERGER, DAVID
GOLTZMAN, DAVID A HANLEY, JONATHAN ADACHI, TENEKE VAN GEEL, PIET GEUSENS, JOOP VAN DEN BERGH,
JACQUELINE CENTER, GARVAN INSTITUTE OF MEDICAL RESEARCH, AUSTRALIA
33
The most parsimonious model predicting premature 5-year mortality included age, current smoking, comorbidities and
fracture type

§  Excessive mortality for the first 5 years post fracture for virtually all incident
low-trauma fractures
§  Increased risk for an additional 5 years after subsequent fracture
§  Need for early intervention to decrease subsequent fracture risk and
potentially mortality
CONCLUSION
PRIOR, ROBERT G JOSSE, STEPHANIE M KAISER, CHRISTOPHER S KOVACS, CLAUDIE BERGER, DAVID
GOLTZMAN, DAVID A HANLEY, JONATHAN ADACHI, TENEKE VAN GEEL, PIET GEUSENS, JOOP VAN DEN BERGH,
JACQUELINE CENTER, GARVAN INSTITUTE OF MEDICAL RESEARCH, AUSTRALIA
34

Reduced Mortality and Subsequent Fracture
Risk with Oral Bisphosphonate Treatment
in Secondary Fracture Prevention
An Observational 8-year Follow-Up Study
LB-‐1153

12
October
2015

Tineke
van
Geel,
Dana
Bliuc,
Piet
Geusens,

Jacqueline
Center,
Geert-‐Jan
Dinant,
Joop
van
den
Bergh,
Alastair

McLellan,
John
Eisman

Faculty of Health, Medicine and Life Sciences
methodsbackground
9439 patients ≥ 50 yrs (1999-2007)
0509 (5.4)0 reviewed
1822 (19.3) frail elderly
2097 (22.2) declined
5011 (53.1) fully assessed; all prescribed CaD
No additional treatment
2477 (49.4%)
+ oral bisphosphonates
2534 (50.6%)
293(11.8)
re-fx
235 (9.5)
deceased
336 (13.3)
re-fx
381 (15.0)
deceased
P = 0.126
P < 0.001

Baseline Characteristics
CaD alone + BP
Women, % 72.4 82.9
Age, years 64.4 73.4
BMD, T-score -1.5 -3.1
Initial hip fx, % 6.2 21.2
P < 0.001
Patients on BP had worse
baseline characteristics
background results

background results
+ BP
CaD alone
Subsequent
fractures
HR: 1.17
(1.00-1.36)
P = 0.056
HR: 0.59
(0.48-0.73)
P < 0.001
Univariable Multivariable

background results
+ BP
CaD alone
Mortality
HR: 1.64
(1.40-1.93)
P < 0.001
Univariable Multivariable
HR: 0.79
(0.64-0.96)
P = 0.021

FR0025 Does Cortical Bone Loss Preceed Menopause?
§  Prospective study: 249 pre-, 32 peri- and 103 postmenopausal women aged 27-75
years at baseline
§  Prospective twin study in Melbourne, Australia
§  173 women remained pre-, 49 changed from pre-to peri-, and 30 from peri- to
postmenopausal
Assess whether cortical bone loss occurs by intracortical and endocortical remodeling
shortly before menopause
PARTICIPANTS
§  2 time points: baseline +3.1 yrs (average)
§  Quantify distal tibia and radius cortical + trabecular bone microarchitecture. Images of
distal tibia by HR-pQCT
DESIGN
§  Total, tb and cort vBMD, cort porosity of the total cortex, compact cortex, outer and
inner transitional zones quantified using the StrAx1.0 software
§  Calculation of annual changes
OUTCOMES
AND ANALYSIS
HR-PQCT high resolution peripheral quantified computer tomography • Tb trabecular • Cort cortical • vBMD volumetric bone mineral density
ASHILD BJORNEREM, ALI GHASEM-ZADEH, ROGER ZEBAZE, XIAOFANG WANG, MINH BUI, JOHN L HOPPER, EGO
SEEMAN, UIT THE ARCTIC UNIVERSITY OF NORWAY, NORWAY

FR0025 Does Cortical Bone Loss Preceed Menopause?
§  Less than 6% of cortical bone is lost before menopause, 94% is during and
after menopause and arise more from the cortical than from the trabecular
compartment
§  We infer that intracortical and endocortical remodeling produces modest
cortical bone loss before menopause, most bone is lost after menopause
and cortical exceeds trabecular bone loss
AUTHOR’S
CONCLUSION
ASHILD BJORNEREM, ALI GHASEM-ZADEH, ROGER ZEBAZE, XIAOFANG WANG, MINH BUI, JOHN L HOPPER, EGO
SEEMAN, UIT THE ARCTIC UNIVERSITY OF NORWAY, NORWAY
42

1054 Effects of Denosumab on Bone Matrix Mineralization: Results
From the Phase 3 FREEDOM Trial.
§  In this analysis, 72 bone biopsy samples (42 DMAb, 30 Pbo) from a subset
of the FREEDOM bone biopsy assessment (N = 115) were evaluated and
analyzed
§  Degree of mineralization of bone (DMB) and the heterogeneity index (HI)
Results
DAVIDW DEMPSTER, JACQUES P BROWN, SUSAN YUE, DELPHINE FARLAY, SEBASTIEN RIZZO, JENNY SONG,
ANDREA WANG, RACHEL B WAGMAN, GEORGES BOIVIN

1054 Effects of Denosumab on Bone Matrix Mineralization: Results
From the Phase 3 FREEDOM Trial.
§  Treatment of women with postmenopausal osteoporosis with DMAb resulted
in increased bone matrix mineralization and a lower HI compared with Pbo.
§  These data are consistent with expected results based on observations with
other antiresorptives (Bala Eur J Endocrinol 2011) and with mechanism of
action
Conclusions
DAVIDW DEMPSTER, JACQUES P BROWN, SUSAN YUE, DELPHINE FARLAY, SEBASTIEN RIZZO, JENNY SONG,
ANDREA WANG, RACHEL B WAGMAN, GEORGES BOIVIN

§  Open-label single-centre study
§  20 postmenopausal women (age 64.4±15.4 years) with osteoporosis (BMD
T score < -2.5 at spine or hip) treated with TPTD (20 µg/d) for 104 weeks
45

Apply a novel patient-specific finite element (FE) model of the disc-vertebra-disc (DVD) unit
to quantify the effect of TPTD on vertebral strength
DESIGN
§  QCT scans of the lumbar spine at baseline, 26, 52 and 104 weeks
§  DVD FE models of the L2 vertebrae generated using brick elements
§  Vertebral strength defined using a 0.2% offset method in the load-
displacement curve
§  Transverse-isotropic, elastic-perfectly plastic material properties at the
vertebra.
§  Linear-elastic properties for the nucleus pulposus and annulus ground
matrix
METHODS
FE finite element • TPTD teriparatide • BMD bone mineral density • QCT quantitative computer tomography • DVD disc-vertebra-disc • L lumbar
FR0028 Effect of Teriparatide Treatment on Vertebral Strength in
Postmenopausal Women with Osteoporosis Assessed Using a Patient-
Specific Finite Element Model of the Disc-Vertebra-Disc Unit
CHUHEE LEE, MARGARET A PAGGIOSI, EUGENE V MCCLOSKEY, NICOLA FA PEEL, JENNIFER S WALSH, RICHARD
EASTELL, LANG YANG, UNIVERSITY OF SHEFFIELD, UK

TPTD teriparatide • FE finite element • DXA dual x-ray absorptiometry • L lumbar • BMD bone mineral density • QCT quantitative computer tomography • v volumetric
46

47

§  Vertebral strength derived from the in vivo DVD FE model shows a larger
treatment effect relative to the baseline value than densitometric variables
§  The present study confirms the major effect of TPTD on bone strength
§  From a clinical point of view these findings reassure us that the patients on
TPTP see antifracture efficacy despite modest increases in BMD
CONCLUSIONS
DVD disc-vertebra-disc • FE finite element • FEA finite element analysis • TPTD teriparatide • BMD bone mineral density • VF vertebral fracture

1055 Effect of Denosumab (DMAB) and Teriparatide (TPTD) Transitions on
Peripheral Bone Mineral Density (BMD) and Microarchitecture: The DATA-
Switch HR-pQCT Study
§  Postmenopausal osteoporotic women with L-spine/Hip T score <1.5; or L-
spine/Hip T score <1.0 with RF; or history of low trauma fracture
Determine the effect of Denosumab (DMAB) and Teriparatide (TPTD) Transitions on
Peripheral Volumetric Bone Mineral Density (vBMD) and Microarchitecture
PARTICIPANTS
Year 1 and 2 Year 3 and 4
TPTD 20µg daily g DMAB 60mg/6-months
DMAB + TPTD g DMAB 60mg/6-months
DMAB 60mg/6-months g TPTD 20µg/day
DESIGN
§  Net gain over 4 years of distal radial and tibial:
•  Tot.vBMD, Tb.vBMD, Ct.vBMD, Ct.Th, trabecular microarchitecture
OUTCOMES
AND ANALYSIS
DMAB denosumab • TPTD teriparatide • BMD bone mineral density • Tot total • v volumetric • Ct cortical • Tb trabecular • Th thickness • HRpQCT high resolution
peripheral computer tomography • RF risk factor
JOY TSAI, ALEXANDER UIHLEIN, SHERRI-ANN BURNETT-BOWIE, ROBERT NEER, PADRIG TUCK, PAUL WALLACE,
MARY BOUXSEIN, BENJAMIN LEDER, MASSACHUSETTS GENERAL HOSPITAL, USA
48
Congress Highlights ASBMR 2015 Annual Meeting

Lancet
2015;
386:
1147–55


Whether TPTD-induced Ct.vBMD decreases represent
as yet under-mineralized new bone is unclear

1055 Effect of Denosumab (DMAB) and Teriparatide (TPTD) Transitions on
Peripheral Bone Mineral Density (BMD) and Microarchitecture: The DATA-
Switch HR-pQCT Study
Comments
Congress Highlights ASBMR 2015 Annual Meeting 52

§  The decline in Ct.vBMD with TPTD after DMAB may represent
accumulation of undermineralised newly formed bone
§  Very small patient numbers limit applicability to clinical practice

MO0335 Biochemical Markers of Bone Turnover and the
Prediction of the BMD Response to Teriparatide, Denosumab
or Both in Postmenopausal Women in the DATA Study
§  94 postmenopausal osteporotic women (age 51-91 years) with no recent
bisphosphonate
Report the relationship between BTMs and BMD in each of the treatment groups
PARTICIPANTS
§  Randomised for 2 years treatment with:
•  TPTD (20µg SC daily)
•  DMAB (60mg SC every 6 months)
•  TPTD (20µg SC daily) + DMAB (60mg SC every 6 months)
DESIGN
§  BMD (DXA) of the hip, spine and 1/3 distal radius at 24 months
§  Serum OC and CTX at 3, 6, 12, 18, and 24 months
§  Pearson’s correlation coefficients & Fisher’s z-transformed normal
approximation
OUTCOMES &
ANALYSIS
BTM bone turnover marker • BMD bone mineral density • TPTD teriparatide • DMAB denosumab • sc sub-cutaneous • OC osteoclacin • CTX collagen type 1
crosslinked C-telopeptide
JOY TSAI, PAUL WALLACE, SHERRI-ANN BURNETT-BOWIE, ALEXANDER UIHLEIN,
ROBERT NEER, HANG LEE, BENJAMIN LEDER, MASSACHUSETTS GENERAL HOSPITAL
HARVARD MEDICAL SCHOOL, USA
53

MO0335 Biochemical Markers of Bone Turnover and the
Prediction of the BMD Response to Teriparatide, Denosumab
or Both in Postmenopausal Women in the DATA Study
§  In women treated with either TPTD or DMAB, early changes in BTMs
predict 2yr BMD gains, especially at the spine
§  In women treated with combination therapy, greater increases in radius
BMD associated with less suppression of bone turnover
§  These results suggest that the superior efficacy of combination therapy at
cortical sites, such as the radius, may depend on persistent bone turnover
despite RANKL inhibition
AUTHOR’S
CONCLUSION
TPTD teriparatide • DMAB denosumab • BTM bone turnover marker
JOY TSAI, PAUL WALLACE, SHERRI-ANN BURNETT-BOWIE, ALEXANDER UIHLEIN,
ROBERT NEER, HANG LEE, BENJAMIN LEDER, MASSACHUSETTS GENERAL HOSPITAL
HARVARD MEDICAL SCHOOL, USA
54

1056 Effect of Odanacatib on Bone Density and Estimated Bone Strength in
Postmenopausal Women: a CT-Based Sub-study of the Phase 3 Long-Term
Odanacatib Fracture Trial (LOFT)
§  164 women (78 ODN, 86 PBO)
Evaluate the effect of ODN on vBMD of trabecular and cortical bone by QCT and estimated
whole-bone strength using FEA
PARTICIPANTS
§  Women ≥65 years
•  Without a baseline radiographic VFx & TH/FN T-score of -2.5 to -4.0
•  With a prior VFx & TH/FN T-score of -1.5 to -4.0
§  ODN 50mg/week or PBO
§  All given vitamin D3 (5600 IU/week) and calcium to achieve ~1200 mg/day
DESIGN
§  Key endpoints: % change from baseline in Tb vBMD at spine and Ct vBMD
at LS and TH after 24 months (assessed by QCT)
§  All endpoints analysed by a Longitudinal Data Analysis model
OUTCOMES
AND ANALYSIS
ODN odanacatib • PBO placebo • VFx vertebral fracture • TH total hip • FN femoral neck • v volumetric • BMD bone mineral density • Tb trabecular • Ct cortical •
QCT quantitative computer tomography • FEA finite element analysis
BENTE LANGDAHL, TOBIAS DEVILLIERS, TONY KEAVENY, KLAUS ENGELKE, HARRY GENANT, SHABANA ATHER, HILDE
GIEZEK, ANTONIO LOMBARDI, ALBERT LEUNG, ANNE DE PAPP, AARHUS UNIVERSITY HOSPITAL, DENMARK
55

RESULTS
ODN odanacatib • PBO placebo • vBMD volumetric bone mineral density • TH total hip • FEA finite element analysis • CI confidence interval • L lumbar
BENTE LANGDAHL, TOBIAS DEVILLIERS, TONY KEAVENY, KLAUS ENGELKE, HARRY GENANT, SHABANA ATHER,
HILDE GIEZEK, ANTONIO LOMBARDI, ALBERT LEUNG, ANNE DE PAPP, AARHUS UNIVERSITY HOSPITAL, DENMARK
56

57

§  In postmenopausal women with osteoporosis, ODN increased both
trabecular and cortical vBMD in the spine and total hip
§  ODN also increased whole-bone strength at the spine and hip as assessed
by finite element analysis
AUTHOR’S
CONCLUSION
ODN odanacatib • vBMD volumetric bone mineral density • TH total hip • FEA finite element analysis
BENTE LANGDAHL, TOBIAS DEVILLIERS, TONY KEAVENY, KLAUS ENGELKE, HARRY GENANT, SHABANA ATHER, HILDE
GIEZEK, ANTONIO LOMBARDI, ALBERT LEUNG, ANNE DE PAPP, AARHUS UNIVERSITY HOSPITAL, DENMARK

1143 Romosozumab Improves Strength at the Lumbar Spine and
Hip in Postmenopausal Women With Low Bone Mass Compared
With Teriparatide
§  Sclerostin is a glycoprotein coded by the SOST gene with significant effects
on bone metabolism
§  Romosozumab is a bone-forming agent that inhibits sclerostin shown to
increase areal BMD (aBMD) in postmenopausal women with low bone mass
§  It has also been shown to have integral volumetric BMD (vBMD) gains at
the spine and hip using quantitative computed tomography imaging
§  This study investigates the effects of romosozumab on bone strength, as
assessed by finite element analysis (FEA) of QCT scans of hip and spine
INTRODUCTION
BMD bone mineral density •a areal • v volumetric • QCT quantitative computer tomography
TONY KEAVENY, DB CRITTENDEN, MA BOLOGNESE, HK GENANT, K ENGELKE, B OLIVERI,
JP BROWN, BL LANGDAHL, YC YANG, A GRAUER, C LIBANATI, UNIVERSITY OF
CALIFORNIA, BERKELEY, USA
58

1143 Romosozumab Improves Strength at the
Lumbar Spine and Hip in Postmenopausal Women
With Low Bone Mass Compared With Teriparatide
§  Postmenopausal women with lumbar spine, total hip, or femoral neck T-
scores ≤–2.0 and ≥–3.5
Investigate the effects of romosozumab on bone strength by FEA
PARTICIPANTS
§  Randomised to
•  Romosozumab 210mg SC monthly (n=24)
•  Teriparatide 20µg daily (open label) (n=27)
•  Placebo (n=31)
DESIGN
§  QCT: L1 & L2 lumbar vertebrae & proximal femur - baseline & 12months
§  Bone strength by 3D FEA (VirtuOst, O.N. Diagnostics)
OUTCOMES
AND ANALYSIS
FEA finite element analysis • sc sub cutaneous • L lumbar • QCT quantitative computer tomography
59

CI confidence interval • FEA finite element analysis
60

Reproduced
with
permission

from
the
American
Society
for
Bone
and
Mineral
Research


§  Romosozumab increased strength at the spine and hip over 12 months, with
strength improving in the “cortical” and trabecular compartments at both
sites
§  These strength improvements support romosozumab evaluation in the
ongoing phase 3 clinical program
AUTHOR’S
CONCLUSION
§  This study provides evidence of a bone strength benefit of romosozumab
compared with placebo at the hip and lumbar spine in keeping
improvemeents in BMD
§  This may result in improved clinical anti-fracture efficacy of romosozumab
CLINICAL
IMPACT FROM
REVIEWER’S
PERSPECTIVE
BMD bone mineral density
61

Back to TOC

1089 Effects of High Dose Vitamin D Supplementation on Bone
metabolism in Pregnant Women with Hypovitaminosis D – a
Randomized Controlled Trial.
§  Investigator-initiated double-blind, randomized, placebo-controlled, parallel-
group trial.
§  Women, aged 20-40 years, with 25OHD < 50 nmol/L
§  all planning pregnancy (N=193)
§  randomized to a daily supplementation with 70 ug (2800 IU), 35 ug (1400
IU) vitamin D3 (VitD3), or placebo.
§  Supplementation initiated before conception and continued until 16 weeks
post partum (PP).
§  Main outcome measures
– BMD
– trabecular bone score (TBS)
– at time of inclusion and four months PP.
GITTE BLOCH RASMUSSEN, LEIF MOSEKILDE, TANJA SIKJAER, PETER VESTERGAARD, LENE HEICKENDORFF,
NIELS ULDBJERG, BENTE LANGDAHL, LARS REJNMARK

§  90 women gave birth
§  Vitamin D supplementation did not affect birth weight
§  25OHD levels increased dosedependently reaching a peak level at the time
of giving birth of 118 nmol/l in the 70 ug and 98nmol/l in the 35 ug/day
group, and 60 nmol/l in the placebo group
§  Four months PP, 86% were breast feeding their infants with no differences
between groups.
§  BMD at most sites and TBS were significantly decreased 16 weeks after
giving birth compared with the pre-pregnancy measurement (p<0.001).
§  Changes in BMD from pre-pregnancy to 16 weeks PP did not differ between
groups at the lumbar spine (p=0.51), total hip (p=0.35), whole body
(p=0.31), or for TBS (p=0.52).
§  At the femoral neck BMD decreased 4.8% in the women treated with 70 ug
compared to placebo (p=0.03).
§  Bone turnover markers during pregnancy and breast feeding did not differ
significantly between groups
Results

§  Pregnant women with vitamin D insufficiency experienced no major
beneficial effects of high dose vitamin D supplementation.
§  The pregnancy associated decrease in BMD was not prevented by vitamin
D supplementation.
§  Our finding of an aggravated BMD loss at the femoral neck in response to a
daily supplement of 70 ug VitD3 calls for caution on use of high dose
vitamin D supplementation during pregnancy.Conclusions

FR0359 Bisphosphonate Therapy, and the Bone Protection Treatment
Care Gap, in Men on Androgen Deprivation Therapy for Non-Metastatic
Prostate Cancer
67
§  Androgen deprivation therapy (ADT) plays a major role in the management
of men with non-metastatic prostate cancer
§  However, its use is associated with high rates of bone loss and an increased
fracture risk
§  A striking evidence-treatment gap exists for bone protection in men
commencing ADT for prostate cancer, where guidelines recommend a bone
health assessment and initiation of treatment at the time of commencement
of ADT
§  There are few data from real world settings determining if bisphosphonate
(BP) treatment reduces fractures in men commencing ADT
INTRODUCTION
BP biphosphonate • ADT androgen deprivation therapy
LISA-ANN FRASER, WESTERN UNIVERSITY, CANADA

Prostate Cancer
§  Population level data from Ontario, Canada
§  Nested case-control study among men >/=66 years diagnosed with PC
§  Event-free controls matched to cases (ratio of 5:1) on age, history of
previous MOF, year of ADT initiation, long-term care (LTC) vs. community
residence
68
Study whether treatment with a BP prevents fractures in men on ADT for non-metastatic
PC
PARTICIPANTS
§  ADT defined as >/=6 months of continuous use of pharmacological ADT or
bilateral orchiectomy
§  Exclusion of men with history of metastasis, or prior BP use
METHOD
§  Conditional logistic regression to estimate the odds ratio of MOF associated
with BP useANALYSES
BP biphosphonate • ADT androgen deprivation therapy • PC prostate cancer • MOF major osteoporotic fracture • LTC long term care

69
§  18,726 men on ADT for non-metastatic PC
- Only 10.4% treated with BP within 3 years of ADT initiation
- 1,298 men experienced a MOF
§  7,780 men with MOF
-  6,490 matched controls
-  1, 298 men on ADT
-  mean age 78.5 (±6) years
-  8.8% had a prior osteoporotic fracture
-  1.1% resided in LTC
§  BP used in 101 (7.8%) of men on ADT and in 363 (5.6%) of controls
§  BP not significantly associated with lower MOF incidence (adjusted
OR=1.29, 95%CI 0.99-1.69)
RESULTS
PC prostate cancer • BP bisphosphonate • ADT androgen deprivation therapy • MOF major osteoporotic fracture • OR odds ratio • CI confidence interval • LTC long
term care
Prostate Cancer

70
§  Over 10 years, there was no reduction in MOF with BP in men with non-
metastatic PC on ADT therapy
§  A bone treatment care gap exists in these men as only 10.4% were
commenced on BP within 3 years of starting ADT
AUTHOR’S
CONCLUSION
§  BP have been shown to prevent bone loss, while denosumab prevents
fractures, in men with non-metastatic PC on ADT therapy
§  Despite effective therapies and guidelines for their use being available, this
study highlights that the majority of men with non-metastatic PC on ADT
therapy are not receiving bone protection
§  Multidisciplinary team approaches combining urologists and radiation
oncologists with bone health experts may overcome this bone treatment
care gap
CLINICAL
PERSPECTIVE
PC prostate cancer • BP bisphosphonate • MOF major osteoporotic fracture • ADT androgen deprivation therapy
Prostate Cancer

FR0323 Skeletal Health in Healthy Postmenopausal Women Treated with
Exemestane for the Primary Prevention of Breast Cancer: 3-year data from the
nested bone strength substudy of the MAP.3 trial (MAP3BSS)
71
INTRODUCTION
AI aromatase inhibitor • BMD bone mineral density
MIRANDA BOGGILD, LIANNE TILE, GEORGE TOMLINSON, NATASHA GAKHAL, SANDHYA PRUTHI, JOHN ROBBINS,
SHAIL RAWAL, SHARMILA MAJUMDAR, SUNDEEP KHOSLA, JAMES INGLE, HARRIET RICHARDSON, PAUL GOSS,
ANGELA CHEUNG, UNIVERSITY OF TORONTO, CANADA
§  Up to 18% of women will sustain a fracture 5-6 years after commencing
aromatase inhibitor (AI) therapy for breast cancer
§  Severe oestrogen deficiency deficiency induced by AI therapy leads to
increased bone remodeling, rapid decreases in BMD, and a rapid increase
in fracture risk
§  As AI therapy is now being used for the primary prevention of breast cancer
in healthy postmenopausal women, it is important to balance the risks of
treatment with its benefits
§  It is therefore important to assess the effects of AI therapy on bone in
healthy postmenopausal women

§  362 postmenopausal women: 171 in exemestane group, 191 placebo
§  79 crossed over from the placebo to the exemestane group after unblinding at 2 years
72
The effect of exemestane (aromatase inhibitor) on bone strength after 3 years of treatment
PARTICIPANTS
§  MAP.3 trial: a placebo-controlled randomized trial
§  Exemestane 25 mg/day for the primary prevention of breast cancer
§  No OP (T-score >-2.0 at all sites)
§  No bone medications
§  No fragility fracture
DESIGN
§  Primary outcome: change from baseline to 3 years in total vBMD at the distal radius
by HRpQCT
§  All outcomes: % change over time between groups with the Kruskal-Wallis test.
OUTCOMES AND
ANALYSIS
Pbo placebo • OP osteoporosis • vBMD volumetric bone mineral density • HRpQCT high resolution peripheral quantitative computer tomography

73
CI confidence interval • HRpQCT high resolution peripheral micro-computed tomography • BMD bone mineral density

74
§  The decline in secondary bone outcomes continued into the
third year and was significantly different compared to the
placebo group
RESULTS
LS lumbar spine • CI confidence interval • v volumetric • a areal • BMD bone mineral density

75
§  Three years of exemestane treatment results in progressive negative effects
on bone, despite calcium and vitamin D supplementation
§  Further and larger studies with long-term follow-up, including fracture risk,
are needed to allow an assessment of the risks and benefits of exemestane
therapy for the primary prevention of breast cancer
AUTHOR’S
CONCLUSION
AI aromatase inhibitor

SYMP Cross talk between kidney and bone: bench to bedside
§  Klotho
– Enzyme, b-glucuronidase
– Expresed in renal proximal tubules
– Coreceptor and activator of FGF receptor
– Adequate amount of Klotho is essential for phosphaturic action of FGF-23
§  FGF-23
– Member of the FGF family
– Endocrine function
– Main function: regulation of phosphate and vitamin D levels in plasma
– Secreted by osteocytes
– Acts on kidneys
– Decreases the reabsorption and increases the excretion of phosphate
– Suppresses vitamin D synthesis
– Has different actions in presence/absence of Klotho
FGF23 AND
KLOTHO
FGF fibroblast growth factor
ORSON MOE ET AL.

Highlights
ASBMR
2015

78

Highlights
ASBMR
2015

79

Komaba,
H.
&
Fukagawa,
M.
(2012)
The
role
of
FGF23
in
CKD—with
or
without
Klotho

Nat.
Rev.
Nephrol.
doi:10.1038/nrneph.2012.116

Klotho-‐dependent
and
Klotho-‐independent
eﬀects
of
FGF23
in
ESRD

80

§  Worldwide epidemic
§  FGF-23 levels increase from stage 1 to stage 5
§  Phosphate levels still normal in stage 4
§  FGF-23, but not Klotho, associated with death or ESRD
§  FGF-23 and risk of cardiovascular events
§  Cardiac disease in CKD
§  RF: hypertension, dyslipidemia, diabetes, smoking, age, high Ca, high P
§  Phosphate levels are highly correlated with vascular calcification
§  Role of Klotho in vascular tissue remains uncertain
CHRONIC
KIDNEY
DISEASE
(CKD)
ESRD end stage renal disease • CKD-MBD chronic kidney disease-mineral and bone disorder • RF Risk factor • FGF fibroblast growth factor • Ca calcium • P
phosphate
ORSON MOE, MICHAEL ECONS, REINHOLD ERBEN, MAKOTO KURO-O, CHRISTIAN FAUL, MYLES WOLF, KEITH
HRUSKA, L DARRYL QUARLES, KENNETH WHITE, CECILIA GIACHELLI, MARK SARNAK, SHARON MOE, TAMARA
ISAKOVA, STUART SPRAGUE SEIJI FUKUMOTO, JOVANA KALUDJEROVIC, LINDSAY COE, SOHEL SHAMSUZZAMAN,
JACKIE FRETZ

Highlights
ASBMR
2015

82

§  ADHR: autosomal dominant hypophosphatemic ricket
Mutation induced impaired cleavage of FGF-23
Incomplete penetrance
Onset in reproductive years
History of waxing and waning due to variations in FGF-23 levels
§  XLH: X-linked hypophosphatemia
Inactive mutation of PHEX
Overproduction of FGF-23
§  TC: tumoral calcinosis
Mutation in GALNT3
Inadequate production of intact FGF-23
GENETIC
DISEASES
ORSON MOE ET AL

Highlights
ASBMR
2015

84

PHEX = phosphate regulating
endopeptidase homolog, X-linked

a genetic disorder that affects
about one in 20,000 people

Lower
limb
deformi5es
(bow-‐knee)

Waddling
gait

Short
stature
or
declining
growth
rate

Spontaneous
tooth
abscesses

Bone
pain

Muscle
pain
and
weakness

Highlights
ASBMR
2015

85

Highlights
ASBMR
2015

86

SA0284 Serum phosphate levels are associated with fracture risk:
the Rotterdam Study
§  Positive association between P and all-type fracture risk in both sexes
§  (men: 1.54(1.20-1.97); women: 1.23(1.01-1.49); sex-combined: 1.35
(1.15-1.58))
§  Similar after adjustments for levels of calcium, 25-OHD, kidney function
(defined as creatinine-based estimated glomerular filtration rate) and BMD
§  or after restricting analyses with subjects with normal kidney function (men
1.81(1.28-2.55); women: 1.25(1.01-1.55)).
§  To conclude, P was negatively related to LS-BMD in men but not women,
and no association with FN-BMD was found in either sex.
§  P was positively related to all-type fracture risk in both sexes.
§  Our findings suggest that increased P even within normal range might be
deleterious for bone health in the normal population
Summary
NATALIA CAMPOS, NADIA KOEK, BRAM C VAN DER EERDEN, FERNANDO RIVADENEIRA, ALBERT HOFMAN,
JOHANNES VAN LEEUWEN, ANDRE G UITTERLINDEN, CAROLA ZILLIKENS

LB-1156 The Association of Race Ethnicity and Risk of Atypical Femur
Fracture in Women Treated with Oral Bisphosphonate Drugs
§  Ethnicity: 65.3% white, 17.1% Asian, 17.6% other races
§  During a median follow-up of 7.7 years
§  68 women with AFF
§  Rate of AFF 18.7 per 100,000 person-years overall
§  8x higher in Asian compared to white women (64.2 vs 7.6 per 100,000
person-years, respectively)
§  Race/ethnicity strongly associated with risk of AFF, with an age-adjusted
relative hazard of 8.5 (95% CI 4.9-14.9) comparing Asian to white women
RESULTS
AFF atypical femoral fracture • BP biphosphonate • RA rheumatoid arthritis • CI confidence Interval
JOAN LO, RITA HUI, CHRISTOPHER GRIMSRUD, MALINI CHANDRA, ROMAIN NEUGEBAUER, JOEL GONZALEZ,
AMER BUDAYR, GENE LAU, BRUCE ETTINGER, KAISER PERMANENTE, USA
90

LB-1156 The Association of Race Ethnicity and Risk of Atypical Femur
Fracture in Women Treated with Oral Bisphosphonate Drugs
§  Overall incidence of AFF was 18.7/ 100,000 person-year
§  Marked racial disparity in AFF risk that should be further examined,
particularly the mechanisms accounting for this difference
§  Median duration of BP treatment was longer and existence of diabetes was
higher in Asian women, which may affect results
§  Counseling of Asian women about osteoporosis drug continuation should
include consideration of their higher AFF risk
CONCLUSION
AFF atypical femoral fracture • BP biphosphonate
JOAN LO, RITA HUI, CHRISTOPHER GRIMSRUD, MALINI CHANDRA, ROMAIN NEUGEBAUER, JOEL GONZALEZ,
AMER BUDAYR, GENE LAU, BRUCE ETTINGER, KAISER PERMANENTE, USA
91

1146 Relationship Between Total Hip BMD T-score and Incidence of
Nonvertebral Fracture With up to 8 Years of Denosumab Treatment
§  3902 women received DMAb for 3 years during the FREEDOM trial
Investigate the relationship between total hip BMD T-score and the incidence of
nonvertebral fracture through 8 years of DMAb therapy
PARTICIPANTS
§  Extension: 2343 women received DMAb for an additional 5 years, for a total
of 8 years DMAbDESIGN
§  A repeated-measures model to estimate each subject’s BMD T-scores at the
time of their nonvertebral fracture.
§  This analysis related time to nonvertebral fracture and total hip BMD T-score
at the time of nonvertebral fracture
METHODS/
ANALYSIS
DMAb denosumab • BMD bone mineral density
SERGE FERRARI, C LIBANATI, CJF LIN, S ADAMI, JACQUES P. BROWN, F COSMAN, E CZERWIŃSKI, LH DE
GREGÓRIO, J MALOUF, J-Y REGINSTER, NS DAIZADEH, A WANG, RB WAGMAN, EM LEWIECKI, GENEVA
UNIVERSITY HOSPITAL AND FACULTY OF MEDICINE, SWITZERLAND
92

RESULTS
BMD bone mineral density
GREGÓRIO, J MALOUF, J-Y REGINSTER, NS DAIZADEH, A WANG, RB WAGMAN, EM LEWIECKI, GENEVA
UNIVERSITY HOSPITAL AND FACULTY OF MEDICINE, SWITZERLAND
93

§  An
inverse
rela5onship
between
total
hip
BMD
T-‐score
(at
the
5me
of
fracture)
and

nonvertebral
fracture
incidence
regardless
of
age
or
prior
fracture


§  Higher total hip BMD T-scores during DMAb treatment associated with a
lower incidence of nonvertebral fractures
§  Importance of BMD measurement in patients on osteoporosis treatment as
a predictor of fracture risk
§  Supportive of the concept that a specific T-score may be used as a practical
goal for therapy
CONCLUSION
§  BMD prior to initiating osteoporosis therapy is a strong predictor of fracture
risk and response to therapy
§  BMD may be an important component in “treat to target” approaches to
osteoporosisCLINICAL
IMPACT
BMD bone mineral density • DMAb denosumab
GREGÓRIO, J MALOUF, J-Y REGINSTER, NS DAIZADEH, A WANG, RB WAGMAN, EM LEWIECKI, GENEVA UNIVERSITY
HOSPITAL AND FACULTY OF MEDICINE, SWITZERLAND
94

SA0330 Anabolism versus Antiresorption (AVA Study): A Comparison of the Mechanism of
Action (MOA) of Teriparatide (TPTD) and Denosumab (DMAb) in Postmenopausal Women
with Osteoporosis Using Quadruple Fluorochrome Labeled Bone Histomorphometry
§  The reported increase in endogenous intact parathyroid hormone (iPTH)
levels 1-3 months after a dose of DMAb, a bone antiresorber, has led to
speculation that elevation in iPTH could result in early anabolic effect
§  The accepted standard for demonstrating anabolic effects on bone is
dynamic tetracycline labelled bone biopsy
§  Tetracycline labelled bone biopsies in a randomized control trial of iv
zoledronic acid vs. teriparatide (SHOTZ) has recently differentiated the
effects of antiresorber (ZOL) from anabolic (teriparatide)
§  Absence of anabolic effect of denosumab will redirect investigators to find
another mechanism for the sustained increases in BMD seen on long-term
denosumab therapy
§  Specific examination of the cortical envelope will help to elucidate the
cortical bone effects of the 2 agents
INTRODUCTION
BMD bone mineral density • DMAb denosumab • iPTH intact parathyroid hormone
DAVID DEMPSTER, HUA ZHOU, ROBERT RECKER, JACQUES P. BROWN, CHRISTOPHER
RECKNOR, E. MICHAEL LEWIECKI, PAUL MILLER, SUDHAKER RAO, DAVID KENDLER, JOHN
KREGE, JAHANGIR ALAM, KATHLEEN TAYLOR, BORIS JANOS, VALERIE RUFF, COLUMBIA
UNIVERSITY, USA
95

Back to TOC

SA0330 Anabolism versus Antiresorption (AVA Study): A Comparison of
the Mechanism of Action (MOA) of Teriparatide (TPTD) and Denosumab
(DMAb) in Postmenopausal Women with Osteoporosis Using Quadruple
Fluorochrome Labeled Bone Histomorphometry
§  35 PMO women
Evaluate the effects of DMAb vs TPTD
PARTICIPANTS
§  TPTD 20 µg/day
§  DMAb 60 mg once
§  Fasting BTMs and iPTH collected at 0, 1, 3, and 6 months
§  Fluorochrome labeling before a trans-iliac bone biopsy at 3 months
DESIGN
§  MS/BS in the cancellous envelope
§  Dynamic and static histomorphometric indices in cancellous, endocortical,
intracortical, and periosteal envelopes
OUTCOMES
AND ANALYSIS
PMO postmenopausal osteoporosis • TPTD teriparatide • DMAb denosumab • BTM bone turnover marker • iPTH intact parathyroid hormone • BL baseline •
MS mineralizing surface • BS bone surface
UNIVERSITY, USA
96

Back to TOC

§  In the DMAb group, intact PTH increased, peaked at month 1, remained
above BL at months 3 and 6
§  Histomorphometric indices of bone formation in the cancellous envelope
were higher in the TPTD than the DMAb group at month 3
§  Except for MAR, these indices increased with TPTD and decreased with
DMAb treatment from BL to month 3
§  Similar findings observed in other envelopes
§  TPTD increased BTMs from BL: P1NP starting at month 1 and CTX starting
at month 3
§  In the DMAb group, P1NP and CTX decreased from BL at all time points
RESULTS
DMAb denosumab • PTH parathyroid hormone • BL baseline • MAR mineral apposition rate • DMAb denosumab • P1NP procollagen type I N-terminal propeptide •
CTX carboxyterminal cross-linking telopeptide of type I collagen • BTM bone turnover marker
UNIVERSITY, USA
97

Back to TOC

MAR mineral apposition rate • MS mineralizing surface • BS bone surface • BFR bone formation rate • Ac.F activation frequency • DMAb denosumab • TPTD
teriparatide
UNIVERSITY, USA
98

Reproduced
with
permission
from
the
American
Society
for
Bone
and
Mineral
Research

Back to TOC

§  First study to use a quadruple fluorochrome labeling method to compare longitudinal
changes between TPTD and DMAb at the tissue level
§  Opposite Mode Of Action (MOA) of the 2 drugs on bone remodeling
§  Increase in intact PTH after DMAb associated with marked decreases in indices of
bone formation in all envelopes, inconsistent with DMAb causing early indirect anabolic
action
§  TPTD increased histomorphometric indices and BTMs of bone formation in all
envelopes, consistent with an anabolic MOA in trabecular and cortical bone
AUTHOR’S
CONCLUSION
§  Histomorphometry did not demonstrate an anabolic effect of denosumab
corresponding to the rise in PTH at month 3 from baseline
§  Iliac crest may not be the ideal site to assess impact of denosumab on
bone modelling (Modeling in monkey femur at stressed sites of femoral
neck)
§  A slow anabolic effect not seen with short term labelling protocols cannot be
excluded
CLINICAL
IMPACT FROM
REVIEWER’S
PERSPECTIVE
TPTD teriparatide • DMAb denosumab • PTH parathyroid hormone • MOA mode of action
UNIVERSITY, USA
99

Back to TOC

SU0352 Effect of Teriparatide or Risedronate on Pertrochanteric Hip
Fractures Recovery: 26-Week Results of a Randomized Clinical Trial
§  171 patients
§  Prospective, randomized, multicenter, active-control trial of 78-wk duration
26-wk interim results of an ongoing, prospective, randomized, multicenter, active-control
trial of 78-wk duration, comparing the effect of TPTD and RIS initiated within 2 weeks after
the surgical treatment of a pertrochanteric hip fracture
PARTICIPANTS
§  Inclusion criteria: BMD T-score <-2.0SD, 25(OH)D >9.2 ng/mL, a recent
pinned pertrochanteric hip fracture
§  Randomized to TPTD:20 µg/d or RIS:35 mg QW
§  Ca and Vit D supplementation
DESIGN
§  Endpoints: function, hip pain, QoL, radiology outcomes, safety
OUTCOMES
AND ANALYSIS
BMD bone mineral density • QoL quality of life • TPTD teriparatide • RIS risedronate
PER ASPENBERG, JORGE MALOUF, UMBERTO TARANTINO, PEDRO A. GARCÍA-HERNÁNDEZ, COSTANTINO
CORRADINI, SOEREN OVERGAARD, JAN STEPAN, LARS BORRIS, ERIC LESPESSAILLES, FREDE FRIHAGEN,
KYRIAKOS PAPAVASILIOU, HELMUT PETTO, JOSÉ RAMÓN CAEIRO, FERNANDO MARIN, ORTHOPAEDIC SURGERY,
LINKÖPING UNIVERSITY, SWEDEN
100

101

§  No differences in
– SF-36 QoL questionnaire
– Charnley’s scale hip pain
– ability to walk or the use of walking aids during follow-up
– radiographic fracture healing at 6 or 26 wk, mechanical failure of the
implant, loss of reduction or non-union
§  Trends to improved TUG and reduced hip pain with teriparatide as
compared to risedronate
§  Similar AEs between groups
§  More frequent hypercalcemia and hyperuricemia in TPTD
§  3 and 8 non-vertebral fractures in the TPTD and RIS group respectively
(p=0.14)
RESULTS
TPTD teriparatide • AE adverse event • RIS risedronate

102

Reproduced
with
permission
from
authors


103

§  Similar results with TPTD or RIS in several fracture-related outcomes
§  TPTD: less hip pain and a shorter time on the TUG test
§  This randomized trial reports interim exploratory outcomes
§  Such analyses may suggest opportunities for the use of anabolic to more
rapidly and effectively mobilize patients subsequent to surgical repair of hip
fracture
CONCLUSION
TPTD teriparatide • RIS risedronate • TUG time up and go

Seminar 28-11-2015 Prof. J. vd Bergh

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (7)

Similar to Seminar 28-11-2015 Prof. J. vd Bergh

Similar to Seminar 28-11-2015 Prof. J. vd Bergh (20)

More from Stichting Interdisciplinaire Werkgroep Osteoporose

More from Stichting Interdisciplinaire Werkgroep Osteoporose (20)

Recently uploaded

Recently uploaded (20)

Seminar 28-11-2015 Prof. J. vd Bergh